Tissue Engineering is a multidisciplinary field encompassing the principles of bioengineering, cell transplantation, and material science. The goal of tissue engineering is to develop tissue substitutes that may be used to restore, maintain, or improve the function of diseased or damaged human tissues. For example, it is contemplated to seed a man-made platform, called a scaffold, with donor cells and/or growth factors. The scaffolds may then be cultured and implanted in the human body to induce and direct the growth of new, healthy tissue. Similarly, scientists are trying to develop implantable, biodegradable devices that would act as drug delivery vessels.
In order to obtain proper tissue ingrowth and ensure desired nutrient/cell delivery using an implanted scaffold, the quality of the scaffold is essential. For example, for purposes of nutrient/cell delivery, pathways must be provided in the scaffold for the nutrients/cells. Consequently, the scaffold must be highly porous and the pores defined by the scaffold must be highly interconnected. However, it can be appreciated that by increasing the porosity of the scaffold, the mechanical properties of the scaffold will correspondingly decrease. Further, it highly desirable for the implanted scaffold to be fabricated from a material, such as a biodegradable polymer, that is gradually absorbed into the human body. By constructing the scaffold from a biodegradable material, it is ensured that only natural tissue remains in the body after a predetermined time period. For example, scaffolds may be fabricated from polylactic acid (PLA), a polyester which degrades within the body to form lactic acid, polyglycolic acid (PGA), polycaprolactone (PCL) or one of a plurality of natural materials such as proteic materials (collagen, fibrin) or polysaccharidic materials (chitosan, glycosaminoglycans). In addition, in drug delivery applications, it is highly desirable for the scaffold to provide a high surface area to volume ratio. Further, it is often desirable for the scaffold to degrade at a desired rate to properly time the release of the drug to be delivered.
In order for biodegradable tissue engineering scaffolds to be routinely used in the medical field, a manufacturing method must be developed to mass produce geometrically complex scaffolds without the use of organic solvents. While several such methods for fabricating scaffolds have been proposed and produced in the laboratory, most of these methods utilize organic solvents which could render the scaffolds unusable for their intended purposes. Further, these prior methods are not practical for mass producing such scaffolds. As such, attempts have been made to fabricate the scaffolds from microcellular injection molding. As is known, microcellular injection molding is an ideal method for manufacturing a high volume of lightweight, highly dimensionally stable foamed parts with complex geometry. However, the achievable porosity of approximately 30% when utilizing present microcellular injection methods for thermoplastic materials falls far below the required porosity for tissue engineering scaffolds, though the percentage of porosity is highly dependent on the type of tissue and mechanical properties required for the specific application.
Therefore, it is a primary object and feature of the present invention to provide a method for mass producing biodegradable structures for tissue engineering and drug delivery applications.
It is a further object and feature of the present invention to provide a method for producing geometrically complex, highly porous and interconnected biodegradable structures for tissue engineering and drug delivery applications.
It is a still further object and feature of the present invention to provide a method for producing biodegradable structures for tissue engineering and drug delivery applications that is simple and inexpensive.
In accordance with the present invention, a method of fabricating a highly porous structure is provided. The method includes the step of compounding a biodegradable polymer, a water-soluble polymer and a porogen to form a composite blend. The composite blend is injected into a mold and processed therein to generate the structure. The structure is then leached in a fluid for a time period.
The method may include the additional step of introducing a gas in a supercritical state into the composite blend prior to processing the mixture in the mold. It is contemplated that the gas be carbon dioxide, the porogen be sodium chloride, the biodegradable polymer be polylactide and the water-soluble polymer be polyvinyl alcohol. The method may include the additional steps of sieving the porogen to a particle size of less than 300 microns and introducing a foaming agent into the composite blend.
In accordance with a further aspect of the present invention, a method of fabricating a highly porous stricture is provided. The method includes the step of compounding a biodegradable polymer, a water-soluble polymer and a porogen to form a composite blend. A foaming agent is dissolved into the composite blend and the composite blend is injected into a mold to form the structure. Thereafter, the structure is leached in a fluid.
The step of dissolving a foaming agent into the composite blend includes the additional step of introducing a gas in a supercritical state into the composite blend and mixing the composite blend. It is contemplated the gas be carbon dioxide, the porogen be sodium chloride, the biodegradable polymer be polylactide and the water-soluble polymer be polyvinyl alcohol. The method may include the additional step of sieving the porogen to a particle size of less than 300 microns.
In accordance with a still further aspect of the present invention, a method of fabricating a highly porous structure is provided. The method includes the step of introducing a foaming agent into a compound that includes a biodegradable polymer, a water-soluble polymer and a porogen. The compound is processed in a mold to form the structure.
The method may include the steps of leaching the structure in a fluid. The step of introducing a foaming agent may include the additional steps of introducing a gas in a supercritical state into the compound and mixing the compound. It is contemplated that the gas be carbon dioxide, the porogen be sodium chloride, the biodegradable polymer be polylactide and the water-soluble polymer be polyvinyl alcohol. The porogen agent may be sieved to a particle size of less than 300 microns.